Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells
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Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells. / Maurer, Stefanie; Kropp, Korbinian Nepomuk; Klein, Gerd; Steinle, Alexander; Haen, Sebastian P; Walz, Juliane S; Hinterleitner, Clemens; Märklin, Melanie; Kopp, Hans-Georg; Salih, Helmut Rainer.
In: ONCOIMMUNOLOGY, Vol. 7, No. 2, 2018, p. e1364827.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells
AU - Maurer, Stefanie
AU - Kropp, Korbinian Nepomuk
AU - Klein, Gerd
AU - Steinle, Alexander
AU - Haen, Sebastian P
AU - Walz, Juliane S
AU - Hinterleitner, Clemens
AU - Märklin, Melanie
AU - Kopp, Hans-Georg
AU - Salih, Helmut Rainer
PY - 2018
Y1 - 2018
N2 - Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, in particular MICA and MICB, on tumor cells, which was mirrored by enhanced release of their soluble ectodomains. Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls. Platelet-mediated NKG2DL-shedding in turn resulted in impaired "induced self" recognition by NK cells as revealed by diminished NKG2D-dependent lysis of tumor cells. Our results indicate that platelet-mediated NKG2DL-shedding may be involved in immune-evasion of (metastasizing) tumor cells from NK cell reactivity.
AB - Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, in particular MICA and MICB, on tumor cells, which was mirrored by enhanced release of their soluble ectodomains. Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls. Platelet-mediated NKG2DL-shedding in turn resulted in impaired "induced self" recognition by NK cells as revealed by diminished NKG2D-dependent lysis of tumor cells. Our results indicate that platelet-mediated NKG2DL-shedding may be involved in immune-evasion of (metastasizing) tumor cells from NK cell reactivity.
U2 - 10.1080/2162402X.2017.1364827
DO - 10.1080/2162402X.2017.1364827
M3 - SCORING: Journal article
C2 - 29308299
VL - 7
SP - e1364827
JO - ONCOIMMUNOLOGY
JF - ONCOIMMUNOLOGY
SN - 2162-402X
IS - 2
ER -